An Adaptive and Iterative Approach for Multiple Sequence Alignment

1. An Adaptive and Iterative Approach for Multiple Sequence Alignment Yi Wang and Kuo-Bin Li Computational Biology and Chemistry, vol.28, pp. 141–148, 2004

2. Abstract Multiple sequence alignment is a basic tool in computational genomics. The art of multiple sequence alignment is about placing gaps. This paper presents a heuristic algorithm that improves multiple protein sequences alignment iteratively. A consistency-based objective function is used to evaluate the candidate moves. During the iterative optimization, well-aligned regions can be detected and kept intact. Columns of gaps will be inserted to assist the algorithm to escape from local optimal alignments.

3. Abstract The algorithm has been evaluated using the BaliBASE (benchmark alignment database ). Results show that the performance of the algorithm does not depend on initial or seed alignments much. Given a perfect consistency library, the algorithm is able to produce alignments that are close to the global optimum. We demonstrate that the algorithm is able to refine alignments produced by other software, including ClustalW, SAGA and T-COFFEE. The program is available upon request.

4. Progressive Vs Iterative • Progressive approach: • Builds up alignment gradually • Unable to adjust previous alignment • Iterative approach: • Based on an initial solution, it attempts to improve alignment iteratively

5. AIMSA features • Our algorithm, adaptive iterative multiple sequence alignment (AIMSA), has been demonstrated to be able to produce high quality alignments consistently using BAliBASE . • Obtains initial solution from progressive alignment • Detects, evaluates and moves block-gaps to improve quality • Enabled to detect and isolate well-aligned regions • Leave local optima by insert temporary column-gaps without damaging the alignment

6. AIMSA Algorithm • Initialization: • Obtain an initial solution using progressive alignment.

7. AIMSA Algorithm

8. Objective Function • COFFEE(Consistency based Objective Function For alignment Evaluation) • Aij is the pairwise projection of sequences i and j obtained from a MSA • Len(Aij) is the length of Aij • Wijis the weight of pairwise alignment on sequences i and j in the library • Score(Aij) is the number of aligned pairs of residues that are shared between Aij and the library

9. Objective Function • Measures overall alignment quality • Evaluates whether a candidate move should be adopted • A local objective function is defined to identify well-aligned regions

10. Exhaustive and Greedy Block-Gap Move • gap 4 is a single-gap block • gaps 0 and 1 is a 1*2 row block • gaps 0 and 2 is a 2*1 column block • gaps 0, 1, 2 and 3 is a 2*2 block • gaps 4 and 5 also forms a 2*1 column block QDF01KHF QDF23KHF QDK4FPFF AESGFKVF EFK567TF AKR8FSFF

11. Exhaustive and Greedy Block-Gap Move • Exhaustively detects all blocks • Attempts to move it to all eligible positions • Computes the corresponding objective values and stores the best move position • After all the blocks have been evaluated, adopts the single move that generates the best improvement

12. Detect Well-Aligned Regions • Sliding-window algorithm • Once a high-score window detected, it seeks to widen it as much as possible • A minimal length as well as a maximal interval length is set ...GARFIELD THE LAST FAST CAT... ...GARFIELD THE VERY FAST CAT...

13. Insert Column-gaps as Buffers • Beside gap-move, insertion and deletion of gaps are necessary on some occasions • However, to insert gaps might damage its following well-aligned regions Someone has reviewed this paper Someone will preview this paper • If simply insert two gaps to align “review” Someone has- -reviewed this paper Someone will preview this paper

14. Insert Column-gaps as Buffers • Instead, columns of gaps could be inserted • Insert column gaps Someone has reviewed ----this paper Someone will preview ----this paper • Move gaps Someone has- -reviewed --this paper Someone will preview- - --this paper • Filter redundant column gaps Someone has- -reviewed this paper Someone will preview- - this paper

15. Well-aligned Region Buffer Poorly-aligned region Buffer Well-aligned Region Randomly Insert Column-gaps • Column-gaps are also inserted randomly so as to facilitate insertion and deletion deep in poorly-aligned regions • A deterministic insertion is possible but inefficient

16. Results--BAliBASE Reference Sets • Reference 1: equidistant sequences of similar length • Reference 2: family versus orphans • Reference 3: equidistant divergent families • Reference 4: N/C-terminal extensions • Reference 5: internal insertions

17. Results

18. Results

19. Results

20. Results

21. Conclusion • AIMSA is an optimization algorithm aimed at finding good alignments. • AIMSA may be used to align multiple sequences of various combinations. • We believe that the ability for AIMSA to obtain good alignments depends on good pairwise libraries and not very much on the initial or seed alignments. • A main disadvantage of AIMSA is being time-consuming, which stems from its iterative nature.